Immunomodulatory compositions comprising microbial entities

Abstract

This disclosure provides for compositions (e.g., pharmaceutical compositions, dietary supplements, medical foods and food stuff), comprising combinations of live microbe populations for the treatment and/or prevention of immune system disorders and conditions related to inflammation, including both pathogen assisted conditions and conditions that are independent of pathogens. Included with the present disclosure are methods for use of the compositions, and methods for selecting microbial entities to formulate the compositions of the disclosure.

1 . A composition formulated for oral administration comprising a combination of at least two heterologous microbes selected from  Lactobacillus harbinensis, Lactobacillus brevis, Lactococcus lactis , and  Bacillus  velezensis, wherein the heterologous microbes are formulated as a synthetic microbial consortium comprising about 1.0×10 8  to about 1.0×10 12  CFU of each of the heterologous microbes, and wherein at least one of the heterologous microbes comprises a 16S rRNA sequence having at least 97%, at least 98%, at least 98.5%, at least 99%, or at least 100% identity to any one of SEQ ID NOs: 43, 198, 221, and 224, formulated in an amount effective to produce an anti-inflammatory effect in a human subject. 
     
     
         2 . The composition of  claim 1 , further comprising a prebiotic selected from the group consisting of oligofructose, a dried fruit or vegetable powder, and combinations thereof. 
     
     
         3 . The composition of  claim 1 , further comprising one or more vitamins, wherein the one or more vitamins are selected from the group consisting of vitamins A, B6, B12, C, D, E, K1, K2, riboflavin, niacin, folic acid, pyridoxine, thiamine, pantothenic acid, biotin, and combinations thereof. 
     
     
         4 . The composition of  claim 1 , wherein producing an anti-inflammatory effect in a mammalian subject comprises reducing the level and/or activity of at least one inflammatory cytokine selected from Table 8 relative to a level and/or activity of the inflammatory cytokine in the serum of the subject; or a tissue of the subject, prior to administering the composition to the subject. 
     
     
         5 . The composition of  claim 4 , wherein the anti-inflammatory effect in a mammalian subject is caused by the production of at least one anti-inflammatory metabolite selected from the group consisting of indole, indole acetic acid (IAA), indole propionic acid (IPA), bacteriocins, antibacterial peptides, serotonin, gamma-aminobutyric acid (GABA), dopamine, melatonin, secondary bile acids, and combinations thereof. 
     
     
         6 . The composition of  claim 1 , wherein administering an effective amount of the composition to a human subject enables the dietary management of at least one symptom in the subject of a rheumatic disease selected from rheumatoid arthritis, spondyloarthritis, and psoriasis. 
     
     
         7 . The composition of  claim 6 , further comprising administering one or more additional agents for the treatment or management of one or more symptoms of rheumatic disease. 
     
     
         8 . The composition of  claim 7 , wherein the one or more additional agents comprises methotrexate. 
     
     
         9 . The composition of  claim 1 , wherein administering an effective amount of the composition to a human subject enables the dietary management of at least one symptom of aging-associated inflammation in a human subject. 
     
     
         10 . The composition of  claim 1 , wherein the composition comprises at least three heterologous microbes selected from  Lactobacillus harbinensis, Lactobacillus brevis, Lactococcus lactis , and  Bacillus velezensis.    
     
     
         11 . A composition formulated for oral administration comprising a combination of at least two heterologous microbes selected from  Lactobacillus brevis, Lactococcus lactis , and  Bacillus  velezensis, wherein the heterologous microbes are formulated as a synthetic microbial consortium comprising about 1.0×10 8  to about 1.0×10 12  CFU of each of the heterologous microbes, and wherein at least one of the heterologous microbes comprises a 16S rRNA sequence having at least 97%, at least 98%, at least 98.5%, at least 99%, or at least 100% identity to any one of SEQ ID NOs: 43, 198, and 224, formulated in an amount effective to produce an anti-inflammatory effect in a human subject. 
     
     
         12 . The composition of  claim 11 , further comprising a prebiotic selected from the group consisting of oligofructose, a dried fruit or vegetable powder, and combinations thereof. 
     
     
         13 . The composition of  claim 11 , further comprising one or more vitamins, wherein the one or more vitamins are selected from the group consisting of vitamins A, B6, B12, C, D, E, K1, K2, riboflavin, niacin, folic acid, pyridoxine, thiamine, pantothenic acid, biotin, and combinations thereof. 
     
     
         14 . The composition of  claim 11 , wherein producing an anti-inflammatory effect in a human subject comprises reducing the level and/or activity of at least one inflammatory cytokine from Table 8 relative to a level and/or activity of the inflammatory cytokine in the serum of the subject; or a tissue of the subject, prior to administering the composition to the subject. 
     
     
         15 . The composition of  claim 11 , wherein administering an effective amount of the composition to a human subject enables the dietary management of at least one symptom in the subject of a rheumatic disease selected from rheumatoid arthritis, spondyloarthritis, and psoriasis. 
     
     
         16 . The composition of  claim 11 , wherein the composition comprises  Lactobacillus brevis, Lactococcus lactis , and  Bacillus  velezensis. 
     
     
         17 . A composition formulated for oral administration comprising a combination of at least two heterologous microbes comprising  Lactobacillus brevis  and  Lactococcus lactis , wherein the heterologous microbes are formulated as a synthetic microbial consortium comprising about 1.0×10 8  to about 1.0×10 12  CFU of each of the heterologous microbes, wherein at least one of the heterologous microbes comprises a 16S rRNA sequence having at least 97%, at least 98%, at least 98.5%, at least 99%, or at least 100% identity to any one of SEQ ID NOs: 43 and 224 formulated in an amount effective to produce an anti-inflammatory effect in a human subject. 
     
     
         18 . The composition of  claim 17 , further comprising a prebiotic selected from the group consisting of oligofructose, a dried fruit or vegetable powder, and combinations thereof. 
     
     
         19 . The composition of  claim 17 , further comprising one or more vitamins, wherein the one or more vitamins are selected from the group consisting of vitamins A, B6, B12, C, D, E, K1, K2, riboflavin, niacin, folic acid, pyridoxine, thiamine, pantothenic acid, biotin, and combinations thereof. 
     
     
         20 . The composition of  claim 17 , wherein producing an anti-inflammatory effect in a human subject comprises reducing the level and/or activity of at least one inflammatory cytokine from Table 8 relative to a level and/or activity of the inflammatory cytokine in the serum of the subject; or a tissue of the subject, prior to administering the composition to the subject.